X-RAY CRYSTALLOGRAPHY AND PROTEIN EXPRESSION

X 射线晶体学和蛋白质表达

• 批准号: 8168790
• 负责人: Patrick J Loll
• 金额: $ 0.01万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-10 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168790
• 关键词: Anesthetics; Antibiotic Resistance; Antibiotics; Area; Bacitracin; Binding; Biochemical; Biological Factors; Carrier Proteins; Cells; Cessation of life; Computer Retrieval of Information on Scientific Projects Database; Crystallization; Crystallography; Development; Disease; Drug effect disorder; Enzymatic Biochemistry; Enzymes; Eye; Funding; General anesthetic drugs; Goals; Grant; Institution; Integral Membrane Protein; Life; MJD1 protein; Machado-Joseph Disease; Membrane; Membrane Proteins; Methodology; Methods; Modeling; Molecular; Molecular Structure; Nerve Degeneration; Neurons; Pharmaceutical Preparations; Polyubiquitin; Process; Protein Biochemistry; Proteins; Research; Research Personnel; Resources; Signal Transduction; Source; Spectrum Analysis; Students; Tyrocidine; United States National Institutes of Health; Vancomycin; X-Ray Crystallography; base; combat; design; fascinate; interest; novel; polyglutamine; protein expression; protein misfolding; ramoplanin; receptor; structural biology; tool; trafficking

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Research in the Loll lab revolves around molecular structure. The underlying goal for all our projects is to understand biologically important processes at the molecular level. Our principal tool is X-ray crystallography; we also devote much energy to protein expression, protein biochemistry, spectroscopy, and enzymology to support the structural efforts. Specific areas of interest include: * Large natural product antibiotics. Loll and students are applying structural, computational, and biophysical methods to deepen our understanding of how antibiotics like vancomycin, ramoplanin, tyrocidine, and bacitracin function. They hope to use this information to design novel drugs to combat antibiotic resistance. * The structural basis of drug action. We are interested in probing the interactions between drugs and their protein targets at the structural level. Currently, they are examining the binding of general anesthetics to model protein targets, with an eye toward elucidating the structural determinants that control anesthetic recognition. * Deubiquitylation by Josephin proteins. Ataxin-3 and other Josephin proteins catalyze the degradation of poly-ubiquitin chains, modulating signals controlling protein breakdown and trafficking. They are using structural and biochemical approaches to study the function of these enzymes. * The molecular mechanism of polyglutamine disease. We are studying ataxin-3, the causative agent of the neurodegenerative Machado-Joseph disease, using structural, ultrastructural, biochemical, and biophysical methods to understand how expansion of polyglutamine tracts leads to protein misfolding, fibril formation, and neuronal death. * The structural biology of membrane proteins. Many of the most fascinating and crucial processes which occur in living cells are modulated by integral membrane proteins. The Loll lab is studying a number of different membrane-bound enzymes, receptors, and transport proteins; in addition, a substantial effort focuses on the development of crystallization methodologies for these molecules.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 洛尔实验室的研究围绕分子结构展开。我们所有项目的根本目标是在分子水平上了解生物学上重要的过程。我们的主要工具是 X 射线晶体学；我们还投入大量精力研究蛋白质表达、蛋白质生物化学、光谱学和酶学，以支持结构研究。具体感兴趣的领域包括： * 大型天然产物抗生素。 Loll 和学生们正在应用结构、计算和生物物理方法来加深我们对万古霉素、雷莫拉宁、酪肽和杆菌肽等抗生素如何发挥作用的理解。他们希望利用这些信息来设计新药来对抗抗生素耐药性。 * 药物作用的结构基础。我们有兴趣在结构水平上探讨药物与其蛋白质靶标之间的相互作用。目前，他们正在研究全身麻醉剂与模型蛋白质靶点的结合，着眼于阐明控制麻醉剂识别的结构决定因素。 * Josephin 蛋白的去泛素化。 Ataxin-3 和其他 Josephin 蛋白催化多聚泛素链的降解，调节控制蛋白质分解和运输的信号。他们正在使用结构和生化方法来研究这些酶的功能。 * 多聚谷氨酰胺疾病的分子机制。我们正在研究 ataxin-3（神经退行性马查多-约瑟夫病的病原体），利用结构、超微结构、生物化学和生物物理方法来了解多聚谷氨酰胺束的扩张如何导致蛋白质错误折叠、原纤维形成和神经元死亡。 * 膜蛋白的结构生物学。活细胞中发生的许多最令人着迷和最关键的过程都是由整合膜蛋白调节的。 Loll 实验室正在研究多种不同的膜结合酶、受体和转运蛋白；此外，大量的努力集中在这些分子的结晶方法的开发上。